Micellar Fd3m cubosomes from monoolein - long chain unsaturated fatty acid mixtures: Stability on temperature and pH response.

HYPOTHESIS: Control of the nanostructure of self-assembled systems may be achieved through manipulation of surfactant molecular packing and interfacial curvature. In order to phase engineer the inverse micellar cubosomes in some monoolein-fatty acid systems, lipids with wedge shaped molecular geometry were incorporated to promote the formation of this phase, that is of interest as potential sustained released nanocarriers. EXPERIMENTS: Liquid crystalline nanoparticle dispersions of monoolein with some cis unsaturated fatty acids were prepared and their partial temperature-composition phase diagrams and structure were established using high throughput Small Angle X-ray Scattering (SAXS) and cryogenic transmission electron microscopy (cryo-TEM). The pH responsiveness of these systems was evaluated in the presence of phosphate buffered saline (PBS). FINDINGS: The partial temperature-composition phase diagrams of five nanoparticle formulations containing monoolein and unsaturated fatty acids were established and identified the presence of micellar cubosomes in each of these systems. The results indicate that temperature, fatty acid concentration and structure, as well as pH all directly impact the formation and stability of this phase. Low energy inverse micellar cubic to emulsion phase transformations were identified in the monoolein with oleic acid and vaccenic acid systems at physiological temperatures that may be advantageous for staged therapeutic release strategies in nanomedicine.

Non-Lamellar Lyotropic Liquid Crystalline Lipid Nanoparticles for the Next Generation of Nanomedicine.

Nonlamellar lyotropic liquid crystalline (LLC) lipid nanomaterials have emerged as a promising class of advanced materials for the next generation of nanomedicine, comprising mainly of amphiphilic lipids and functional additives self-assembling into two- and three-dimensional, inverse hexagonal, and cubic nanostructures. In particular, the lyotropic liquid crystalline lipid nanoparticles (LCNPs) have received great interest as nanocarriers for a variety of hydrophobic and hydrophilic small molecule drugs, peptides, proteins, siRNAs, DNAs, and imaging agents. Within this space, there has been a tremendous amount of effort over the last two decades elucidating the self-assembly behavior and structure-function relationship of natural and synthetic lipid-based drug delivery vehicles in vitro, yet successful clinical translation remains sparse due to the lack of understanding of these materials in biological bodies. This review provides an overview of (1) the benefits and advantages of using LCNPs as drug delivery nanocarriers, (2) design principles for making LCNPs with desirable functionalities for drug delivery applications, (3) current understanding of the LLC material-biology interface illustrated by more than 50 in vivo, preclinical studies, and (4) current patenting and translation activities in a pharmaceutical context. Together with our perspectives and expert opinions, we anticipate that this review will guide future studies in developing LCNP-based drug delivery nanocarriers with the objective of translating them into a key player among nanoparticle platforms comprising the next generation of nanomedicine for disease therapy and diagnosis.

Paclitaxel-Loaded Self-Assembled Lipid Nanoparticles as Targeted Drug Delivery Systems for the Treatment of Aggressive Ovarian Cancer.

Chemotherapy using cytotoxic agents, such as paclitaxel (PTX), is one of the most effective treatments for advanced ovarian cancer. However, due to nonspecific targeting of the drug and the presence of toxic solvents required for dissolving PTX prior to injection, there are several serious side effects associated with this treatment. In this study, we explored self-assembled lipid-based nanoparticles as PTX carriers, which were able to improve its antitumour efficacy against ovarian cancer. The nanoparticles were also functionalized with epidermal growth factor receptor (EGFR) antibody fragments to explore the benefit of tumor active targeting. The formulated bicontinuous cubic- and sponge-phase nanoparticles, which were stabilized by Pluronic F127 and a lipid poly(ethylene glycol) stabilizer, showed a high capacity of PTX loading. These PTX-loaded nanoparticles also showed significantly higher cytotoxicity than a free drug formulation against HEY ovarian cancer cell lines in vitro. More importantly, the nanoparticle-based PTX treatments, with or without EGFR targeting, reduced the tumor burden by 50% compared to PTX or nondrug control in an ovarian cancer mouse xenograft model. In addition, the PTX-loaded nanoparticles were able to extend the survival of the treatment groups by up to 10 days compared to groups receiving free PTX or nondrug control. This proof-of-concept study has demonstrated the potential of these self-assembled lipid nanomaterials as effective drug delivery nanocarriers for poorly soluble chemotherapeutics, such as PTX.

Manipulating the Ordered Nanostructure of Self-Assembled Monoolein and Phytantriol Nanoparticles with Unsaturated Fatty Acids.

Mesophase structures of self-assembled lyotropic liquid crystalline nanoparticles are important factors that directly influence their ability to encapsulate and release drugs and their biological activities. However, it is difficult to predict and precisely control the mesophase behavior of these materials, especially in complex systems with several components. In this study, we report the controlled manipulation of mesophase structures of monoolein (MO) and phytantriol (PHYT) nanoparticles by adding unsaturated fatty acids (FAs). By using high throughput formulation and small-angle X-ray scattering characterization methods, the effects of FAs chain length, cis-trans isomerism, double bond location, and level of chain unsaturation on self-assembled systems are determined. Additionally, the influence of temperature on the phase behavior of these nanoparticles is analyzed. We found that in general, the addition of unsaturated FAs to MO and PHYT induces the formation of mesophases with higher Gaussian surface curvatures. As a result, a rich variety of lipid polymorphs are found to correspond with the increasing amounts of FAs. These phases include inverse bicontinuous cubic, inverse hexagonal, and discrete micellar cubic phases and microemulsion. However, there are substantial differences between the phase behavior of nanoparticles with trans FA, cis FAs with one double bond, and cis FAs with multiple double bonds. Therefore, the material library produced in this study will assist the selection and development of nanoparticle-based drug delivery systems with desired mesophase.

Self-assembled Lyotropic Liquid Crystalline Phase Behavior of Monoolein-Capric Acid-Phospholipid Nanoparticulate Systems.

We report here the lyotropic liquid crystalline phase behavior of two lipid nanoparticulate systems containing mixtures of monoolein, capric acid, and saturated diacyl phosphatidylcholines dispersed by the Pluronic F127 block copolymer. Synchrotron small-angle X-ray scattering (SAXS) was used to screen the phase behavior of a library of lipid nanoparticles in a high-throughput manner. It was found that adding capric acid and phosphatidylcholines had opposing effects on the spontaneous membrane curvature of the monoolein lipid layer and hence the internal mesophase of the final nanoparticles. By varying the relative concentration of the three lipid components, we were able to establish a library of nanoparticles with a wide range of mesophases including at least the inverse bicontinuous primitive and double diamond cubic phases, the inverse hexagonal phase, the fluid lamellar phase, and possibly other phases. Furthermore, the in vitro cytotoxicity assay showed that the endogenous phospholipid-containing nanoparticles were less toxic to cultured cell lines compared to monoolein-based counterparts, improving the potential of the nonlamellar lipid nanoparticles for biomedical applications.

High-Throughput Screening of Saturated Fatty Acid Influence on Nanostructure of Lyotropic Liquid Crystalline Lipid Nanoparticles.

Self-assembled lyotropic liquid crystalline lipid nanoparticles have been developed for a wide range of biomedical applications with an emerging focus for use as delivery vehicles for drugs, genes, and in vivo imaging agents. In this study, we report the generation of lipid nanoparticle libraries with information regarding mesophase and lattice parameter, which can aid the selection of formulation for a particular end-use application. In this study we elucidate the phase composition parameters that influence the internal structure of lipid nanoparticles produced from monoolein, monopalmitolein and phytantriol incorporating a variety of saturated fatty acids (FA) with different chain lengths at varying concentrations and temperatures. The material libraries were established using high throughput formulation and screening techniques, including synchrotron small-angle X-ray scattering. The results demonstrate the rich polymorphism of lipid nanoparticles with nonlamellar mesophases in the presence of saturated FAs. The inclusion of saturated FAs within the lipid nanoparticles promotes a gradual phase transition at all temperatures studied toward structures with higher negative surface curvatures (e.g., from inverse bicontinuous cubic phase to hexagonal phase and then emulsified microemulsion). The three partial phase diagrams produced are discussed in terms of the influence of FA chain length and concentration on nanoparticle internal mesophase structure and lattice parameters. The study also highlights a compositionally dependent coexistence of multiple mesophases, which may indicate the presence of multicompartment nanoparticles containing cubic/cubic and cubic/hexagonal mesophases.

Lipid-PEG conjugates sterically stabilize and reduce the toxicity of phytantriol-based lyotropic liquid crystalline nanoparticles.

Lyotropic liquid crystalline nanoparticle dispersions are of interest as delivery vectors for biomedicine. Aqueous dispersions of liposomes, cubosomes, and hexosomes are commonly stabilized by nonionic amphiphilic block copolymers to prevent flocculation and phase separation. Pluronic stabilizers such as F127 are commonly used; however, there is increasing interest in using chemically reactive stabilizers for enhanced functionalization and specificity in therapeutic delivery applications. This study has explored the ability of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine conjugated with poly(ethylene glycol) (DSPE-PEGMW) (2000 Da ≤ MW ≤ 5000 Da) to engineer and stabilize phytantriol-based lyotropic liquid crystalline dispersions. The poly(ethylene glycol) (PEG) moiety provides a tunable handle to the headgroup hydrophilicity/hydrophobicity to allow access to a range of nanoarchitectures in these systems. Specifically, it was observed that increasing PEG molecular weight promotes greater interfacial curvature of the dispersions, with liposomes (Lα) present at lower PEG molecular weight (MW 2000 Da), and a propensity for cubosomes (QII(P) or QII(D) phase) at MW 3400 Da or 5000 Da. In comparison to Pluronic F127-stabilized cubosomes, those made using DSPE-PEG3400 or DSPE-PEG5000 had enlarged internal water channels. The toxicity of these cubosomes was assessed in vitro using A549 and CHO cell lines, with cubosomes prepared using DSPE-PEG5000 having reduced cytotoxicity relative to their Pluronic F127-stabilized analogues.

Positron annihilation lifetime spectroscopy (PALS): a probe for molecular organisation in self-assembled biomimetic systems.

Positron annihilation lifetime spectroscopy (PALS) has been shown to be highly sensitive to conformational, structural and microenvironmental transformations arising from subtle geometric changes in molecular geometry in self-assembling biomimetic systems. The ortho-positronium (oPs) may be considered an active probe that can provide information on intrinsic packing and mobility within low molecular weight solids, viscous liquids, and soft matter systems. In this perspective we provide a critical overview of the literature in this field, including the evolution of analysis software and experimental protocols with commentary upon the practical utility of PALS. In particular, we discuss how PALS can provide unique insight into the macroscopic transport properties of several porous biomembrane-like nanostructures and suggest how this insight may provide information on the release of drugs from these matrices to aid in developing therapeutic interventions. We discuss the potentially exciting and fruitful application of this technique to membrane dynamics, diffusion and permeability. We propose that PALS can provide novel molecular level information that is complementary to conventional characterisation techniques.

The effect of structural modifications on the solution and interfacial properties of straight and branched aliphatic alcohols: the role of hydrophobic effects.

The effect of structural modifications, such as branching of the hydrocarbon chain on the solution and interfacial properties of short-chain aliphatic alcohols has been investigated. Surface tension measurements have been used to study the adsorption of the alcohols at the aqueous solution/air interface from water/alcohol mixtures, and to determine the aqueous solubilities of the alcohols. The related process of the partitioning behaviour of the alcohols between two immiscible phases has also been studied. Standard free energies of adsorption at the aqueous solution/air interface, standard free energies of transfer between water and hexane, and standard free energies of solution were obtained for the alcohols. A linear "Traube" relationship, an elegant demonstration of the hydrophobic effect, was found to exist between the various free energies for the normal alcohols and the number of carbon atoms in the alcohol molecule. The free energies showed that structurally modified alcohols have less negative free energy of adsorption, transfer or solution compared to the normal alcohol with the same number of carbon atoms. We assign effective numbers of carbon atoms for each branched alcohol for each transfer process. The position of the hydroxyl group relative to the branched part of the molecule was found to be a factor which influences the hydrophobic contribution to the free energy of each transfer process. An attempt has been made to ascertain whether there is a correlation between the molecular surface area, or the molecular volume, and the interfacial and solution thermodynamic properties of an alcohol in aqueous solution. The standard free energies of some of the branched alcohols have been found to be inconsistent with the values expected from the energetic of the adsorption and the water/hexane transfer processes. This is thought to reflect the different modes of association of the branched and normal alcohols in the liquid state as revealed by small and wide angle X-ray scattering which identifies correlation peaks attributable to intermolecular hydrogen bonding and interchain associations consistent with non-polar segmentation.

Application of positron annihilation lifetime spectroscopy (PALS) to study the nanostructure in amphiphile self-assembly materials: phytantriol cubosomes and hexosomes.

Self-assembled amphiphile nanostructures of colloidal dimensions such as cubosomes and hexosomes are of interest as delivery vectors in pharmaceutical and nanomedicine applications. Translation would be assisted through a better of understanding of the effects of drug loading on the internal nanostructure, and the relationship between this nanostructure and drug release profile. Positron annihilation lifetime spectroscopy (PALS) is sensitive to local microviscosity and is used as an in situ molecular probe to examine the Q2 (cubosome) → H2 (hexosome) → L2 phase transitions of the pharmaceutically relevant phytantriol-water system in the presence of a model hydrophobic drug, vitamin E acetate (VitEA). It is shown that the ortho-positronium lifetime (τ) is sensitive to molecular packing and mobility and this has been correlated with the rheological properties of individual lyotropic liquid crystalline mesophases. Characteristic PALS lifetimes for L2 (τ4∼ 4 ns) ∼ H2 (τ4∼ 4 ns) > Q(2 Pn3m) (τ4∼ 2.2 ns) are observed for the phytantriol-water system, with the addition of VitEA yielding a gradual increase in τ from τ∼ 2.2 ns for cubosomes to τ∼ 3.5 ns for hexosomes. The dynamic chain packing at higher temperatures and in the L2 and H2 phases is qualitatively less "viscous", consistent with rheological measurements. This information offers increased understanding of the relationship between internal nanostructure and species permeability.

Packing and mobility of hydrocarbon chains in phospholipid lyotropic liquid crystalline lamellar phases and liposomes: characterisation by positron annihilation lifetime spectroscopy (PALS).

Lipid lamellar mesophases and their colloidal dispersions (liposomes) are increasingly being deployed in vivo as drug delivery vehicles, and also as models of biological membranes in fundamental biophysics studies. The permeability and diffusion of small molecules such as drugs is accommodated by a change in local curvature and molecular packing (mesophase behaviour) of the bilayer membrane molecules. Positron annihilation lifetime spectroscopy (PALS) is capable of providing in situ molecular level information on changes in free volume and void space arising from such changes in a non-perturbative manner. In this work PALS was used to systematically characterise the temperature-induced melting transitions (Tm) of saturated and unsaturated phospholipid-water systems while systematically varying lipid chain length, as both bulk lamellar mesophase and as aqueous colloidal dispersions (liposomes). A four-component fit of the data was used that provides separate PALS lifetimes for the aqueous (τ3) and organic domains (τ4). The oPs lifetime (τ4), for the lamellar phases of DSPC (C18:0), DPPC (C16:0), DMPC (C14:0) and DLPC (C12:0) was found to be independent of chain length, with characteristic lifetime value τ4 ∼ 3.4 ns. τ4 is consistently larger in the dispersed liposomes compared to the bulk mesophases, suggesting that the hydrocarbon chains are more mobile. The use of contemporary and consistent analytical approaches as described in this study is the key to future deployment of PALS to interrogate the in situ influence of drugs on membrane and cellular microenvironments.

Probing the amphiphile micellar to hexagonal phase transition using Positron Annihilation Lifetime Spectroscopy.

Positron Annihilation Lifetime Spectroscopy (PALS) has been utilised only sparingly for structural characterisation in self assembled materials. Inconsistencies in approaches to experimental configuration and data analysis between studies has complicated comparisons between studies, meaning that the technique has not provided a cohesive data set across the study of different self assembled systems that advance the technique towards an important tool in soft matter research. In the current work a systematic study was conducted using ionic and non-ionic micellar systems with increasing surfactant concentration to probe positron behaviour on changes between micellar phase structures, and data analysed using contemporary approaches to fit four component spectra. A characteristic orthopositronium lifetime (in the organic regions) of 3.5±0.2 ns was obtained for the hexagonal phase for surfactants with C12 alkyl chains. Chemical quenching of the positron species was also observed for systems with ionic amphiphiles. The application of PALS has also highlighted an inconsistency in the published phase diagram for the octa(ethylene oxide) monododecyl ether (C12EO8) system. These results provide new insight into how the physical properties of micellar systems can be related to PALS parameters and means that the PALS technique can be applied to other more complex self-assembled amphiphile systems.

High-throughput development of amphiphile self-assembly materials: fast-tracking synthesis, characterization, formulation, application, and understanding.

Amphiphile self-assembly materials, which contain both a hydrophilic and a hydrophobic domain, have great potential in high-throughput and combinatorial approaches to discovery and development. However, the materials chemistry community has not embraced these ideas to anywhere near the extent that the medicinal chemistry community has. While this situation is beginning to change, extracting the full potential of high-throughput approaches in the development of self-assembling materials will require further development in the synthesis, characterization, formulation, and application domains. One of the key factors that make small molecule amphiphiles prospective building blocks for next generation multifunctional materials is their ability to self-assemble into complex nanostructures through low-energy transformations. Scientists can potentially tune, control, and functionalize these structures, but only after establishing their inherent properties. Because both robotic materials handling and customized rapid characterization equipment are increasingly available, high-throughput solutions are now attainable. These address traditional development bottlenecks associated with self-assembling amphiphile materials, such as their structural characterization and the assessment of end-use functional performance. A high-throughput methodology can help streamline materials development workflows, in accord with existing high-throughput discovery pipelines such as those used by the pharmaceutical industry in drug discovery. Chemists have identified several areas that are amenable to a high-throughput approach for amphiphile self-assembly materials development. These allow an exploration of not only a large potential chemical, compositional, and structural space, but also material properties, formulation, and application variables. These areas of development include materials synthesis and preparation, formulation, characterization, and screening performance for the desired end application. High-throughput data analysis is crucial at all stages to keep pace with data collection. In this Account, we describe high-throughput advances in the field of amphiphile self-assembly, focusing on nanostructured lyotropic liquid crystalline materials, which form when amphiphiles are added to a polar solvent. We outline recent progress in the automated preparation of amphiphile molecules and their nanostructured self-assembly systems both in the bulk phase and in dispersed colloidal particulate systems. Once prepared, we can structurally characterize these systems by establishing phase behavior in a high-throughput manner with both laboratory (infrared and light polarization microscopy) and synchrotron facilities (small-angle X-ray scattering). Additionally, we provide three case studies to demonstrate how chemists can use high-throughput approaches to evaluate the functional performance of amphiphile self-assembly materials. The high-throughput methodology for the set-up and characterization of large matrix in meso membrane protein crystallization trials can illustrate an application of bulk phase self-assembling amphiphiles. For dispersed colloidal systems, two nanomedicine examples highlight advances in high-throughput preparation, characterization, and evaluation: drug delivery and magnetic resonance imaging agents.

Direct force measurement between bio-colloidal Giardia lamblia cysts and colloidal silicate glass particles.

Force-separation measurements between Giardia lamblia cysts and an inorganic oxide (silicate glass) have been obtained by using an atomic force microscope (AFM). The cysts are compressible on the scale of the loads applied during force measurement, with the surface compressibility expressed in terms of an interfacial spring constant (K(int)). The force of interaction prior to this Hookean region, on approach, is long-range and repulsive. The long-range force has been compared to models of the electrical double layer as well as an electrosteric layer. The comparison has led to the conclusion that the cyst surface can be described as a polyelectrolyte brush at intermediate separations (5-115 nm from linear compliance) with an electrical double layer often observed at larger separations. The dependence of the interaction force on surface retraction suggests that tethering between the cyst and siliceous surface can occur. The variation of the interaction with pH and upon variation with ionic strength has also been assessed. The information gained from the measurement of the interaction between G. lamblia and this model sandlike surface informs water treatment processes. Similar studies have been performed by us for the Cryptosporidium parvum (C. parvum) oocyst system to which this work is compared.

Lyotropic liquid crystalline phase behaviour in amphiphile-protic ionic liquid systems.

Approximate partial phase diagrams for nine amphiphile-protic ionic liquid (PIL) systems have been determined by synchrotron source small angle X-ray scattering, differential scanning calorimetry and cross polarised optical microscopy. The binary phase diagrams of some common cationic (hexadecyltrimethyl ammonium chloride, CTAC, and hexadecylpyridinium bromide, HDPB) and nonionic (polyoxyethylene (10) oleyl ether, Brij 97, and Pluronic block copolymer, P123) amphiphiles with the PILs, ethylammonium nitrate (EAN), ethanolammonium nitrate (EOAN) and diethanolammonium formate (DEOAF), have been studied. The phase diagrams were constructed for concentrations from 10 wt% to 80 wt% amphiphile, in the temperature range 25 °C to >100 °C. Lyotropic liquid crystalline phases (hexagonal, cubic and lamellar) were formed at high surfactant concentrations (typically >50 wt%), whereas at <40 wt%, only micelles or polydisperse crystals were present. With the exception of Brij 97, the thermal stability of the phases formed by these surfactants persisted to temperatures above 100 °C. The phase behaviour of amphiphile-PIL systems was interpreted by considering the PIL cohesive energy, liquid nanoscale order, polarity and ionicity. For comparison the phase behaviour of the four amphiphiles was also studied in water.

One step multifunctional micropatterning of surfaces using asymmetric glow discharge plasma polymerization.

Micropatterning of surfaces with varying chemical, physical and topographical properties usually requires a number of fabrication steps. Herein, we describe a micropatterning technique based on plasma enhanced chemical vapour deposition (PECVD) that deposits both protein resistant and protein repellent surface chemistries in a single step. The resulting multifunctional, selective surface chemistries are capable of spatially controlled protein adhesion, geometric confinement of cells and the site specific confinement of enzyme mediated peptide self-assembly.

An X-ray and neutron reflectometry study of 'PEG-like' plasma polymer films.

Plasma-enhanced chemical vapour-deposited films of di(ethylene glycol) dimethyl ether were analysed by a combination of X-ray photoelectron spectroscopy, atomic force microscopy, quartz crystal microbalance with dissipation monitoring (QCM-D), X-ray and neutron reflectometry (NR). The combination of these techniques enabled a systematic study of the impact of plasma deposition conditions upon resulting film chemistry (empirical formula), mass densities, structure and water solvation, which has been correlated with the films' efficacy against protein fouling. All films were shown to contain substantially less hydrogen than the original monomer and absorb a vast amount of water, which correlated with their mass density profiles. A proportion of the plasma polymer hydrogen atoms were shown to be exchangeable, while QCM-D measurements were inaccurate in detecting associated water in lower power films that contained loosely bound material. The higher protein resistance of the films deposited at a low load power was attributed to its greater chemical and structural similarity to that of poly(ethylene glycol) graft surfaces. These studies demonstrate the utility of using X-ray and NR analysis techniques in furthering the understanding of the chemistry of these films and their interaction with water and proteins.

Lyotropic liquid crystal engineering-ordered nanostructured small molecule amphiphile self-assembly materials by design.

Future nanoscale soft matter design will be guided to a large extent by the teachings of amphiphile (lipid or surfactant) self-assembly. Ordered nanostructured lyotropic liquid crystalline mesophases may form in select mixtures of amphiphile and solvent. To reproducibly engineer the low energy amphiphile self-assembly of materials for the future, we must first learn the design principles. In this critical review we discuss the evolution of these design rules and in particular discuss recent key findings regarding (i) what drives amphiphile self-assembly, (ii) what governs the self-assembly structures that are formed, and (iii) how can amphiphile self-assembly materials be used to enhance product formulations, including drug delivery vehicles, medical imaging contrast agents, and integral membrane protein crystallisation media. We focus upon the generation of 'dilutable' lyotropic liquid crystal phases with two- and three-dimensional geometries from amphiphilic small molecules (225 references).

Monodisperse nonionic isoprenoid-type hexahydrofarnesyl ethylene oxide surfactants: high throughput lyotropic liquid crystalline phase determination.

The neat and lyotropic phase behavior of eight new ethylene oxide amphiphiles (EO = 1-8) with a hexahydrofarnesyl chain (3,7,11-trimethyldodecyl) and narrow polydispersity (>98.5% purity) is reported. Below five EO units the behavior of the neat surfactants show only a glass transition, Tg ∼ -90 °C. Above four EO units, crystallization (Tcrys) and crystal-isotropic liquid (Tm) transitions are also observed that increase with degree of ethoxylation of the surfactant headgroup. The lyotropic liquid crystalline phase behavior spans a complex spectrum of surfactant-water interfacial curvatures. Specifically, inverse phases are present below ambient temperatures for EO < 4, with HFarn(EO)2 exhibiting an inverse hexagonal (H(II)) phase stable to dilution. The phase diagram of HFarn(EO)3 displays both the gyroid (Ia3d) and double diamond (Pn3m) inverse bicontinuous cubic phases, with the latter being thermodynamically stable in excess water within the physiological regime. There is a strong preference for planar bilayer structures at intermediate headgroup ethoxylation, with the crossover to normal phases occurring at HFarn(EO)(7-8) which exhibits normal hexagonal (H(I)) and cubic (Q(I)) phases at ambient temperatures. The toxicity of colloidal dispersions of these EO amphiphiles was assayed against normal breast epithelial (HMEpiC) and breast cancer (MCF7) cell lines. The IC50 of the EO amphiphiles was similar in both cell lines with moderate toxicity ranging from ca. <5 to 140 µM in an in vitro cell viability assay. Observations are qualitatively rationalized in terms of the molecular geometry of the surfactant. The physicochemical behavior of the HFarnesyl ethylene oxide amphiphiles is compared to other ethylene oxide surfactants.

One-step method for generating PEG-like plasma polymer gradients: chemical characterization and analysis of protein interactions.

In this work we report a one-step method for the fabrication of poly(ethylene glycol) PEG-like chemical gradients, which were deposited via continuous wave radio frequency glow discharge plasma polymerization of diethylene glycol dimethyl ether (DG). A knife edge top electrode was used to produce the gradient coatings at plasma load powers of 5 and 30 W. The chemistry across the gradients was analyzed using a number of complementary techniques including spatially resolved synchrotron source grazing incidence FTIR microspectroscopy, X-ray photoelectron spectroscopy (XPS) and synchrotron source near edge X-ray absorption fine structure (NEXAFS) spectroscopy. Gradients deposited at lower load power retained a higher degree of monomer like functionality as did the central region directly underneath the knife edge electrode of each gradient film. Surface derivatization experiments were employed to investigate the concentration of residual ether units in the films. In addition, surface derivatization was used to investigate the reactivity of the gradient films toward primary amine groups in a graft copolymer of poly (L-lysine) and poly(ethylene glycol) (PLL-g-PEG copolymer) which was correlated to residual aldehyde, ketone and carboxylic acid functionalities within the films. The protein adsorption characteristics of the gradients were analyzed using three proteins of varying size and charge. Protein adsorption varied and was dependent on the chemistry and the physical properties (such as size and charge) of the proteins. A correlation between the concentration of ether functionality and the protein fouling characteristics along the gradient films was observed. The gradient coating technique developed in this work allows for the efficient and high-throughput study of biomaterial gradient coating interactions.